August/September 2020 Issue

Obesity’s Link to Genetics and the Environment
By KC Wright, MS, RDN
Today’s Dietitian
Vol. 22, No. 7, P. 46

Today’s Dietitian explores these two influences and how they may help reduce weight stigma in dietetics practice.

Obesity is a common yet complex condition, and it’s become a grave public health concern worldwide1; both overweight and obesity are risk factors for hypertension, diabetes, and certain cancers and can lead to mental health issues and social stigma.2-4

Moreover, obesity has become ubiquitous, without geographic or demographic boundaries. The global incidence of obesity has tripled in the past four decades as a result of changes in our environment—the physical, social, political, and economic factors that influence how much we eat and move.5 In this obesogenic environment, an excess of calorie-dense foods prevails and lifestyles are marked by physical inactivity. In 2016, approximately 13% of the world’s population had obesity (11% male, 15% female).1 If obesity continues to rise at a similar rate, by 2030, 20% and 38% of the world’s adult population will have obesity and overweight, respectively.6

Weight bias toward individuals with obesity is pervasive and justified by what many perceive as a lack of personal responsibility among those with the condition.4 Evidence suggests the media is a significant source of weight stigma,7 but bias also is common among health care providers, including physicians, nurses, dietitians, and mental health professionals.

This stigma remains despite the known genetic predisposition in some individuals to gain weight more easily than others or store weight around their midsections.2 Heredity influences every aspect of our physiology, development, and adaptation, and weight is no exception. Genetic studies have helped identify the many reasons why some people are more likely than others to have obesity. Emerging research has shown that beyond environmental influences, DNA also determines obesity. Estimates suggest between 40% and 70% of obesity is inherited.8

Thus, the familiar and seemingly simple advice to eat less and move more may not necessarily be successful as a one-size-fits-all approach to healthy weight management. This article reviews investigations to date on the contribution of genes and interactions between genes and the environment on the development of obesity.

Gene Variants and Types of Obesity
The search for the human obesity gene began several decades ago when advances in molecular biology and findings of the Human Genome Project made it possible to link certain genetic factors with obesity. Hundreds of genes have been identified that can contribute to obesity risk. Individually, most of these genes have minimal effect but, when combined, can increase risk significantly.

A literature review on the familial resemblance of BMI and other adiposity measures suggests that genetic factors play a significant role in individual differences in relative body weight and human adiposity. Twin studies suggest a strong genetic influence on BMI with data from more than 25,000 twin pairs and 50,000 biological and adoptive family members. The estimates for mean correlations for BMI are 0.74 for identical twins, 0.32 for fraternal twins, 0.25 for siblings, 0.19 for parent-offspring pairs, 0.06 for adoptive relatives, and 0.12 for spouses.9

In other research, different types of obesity were considered after surveying patients with a minimum BMI of 30. Survey questions included items such as age, demographics, ethnicity, existing health conditions, physical activity, alcohol consumption, and smoking status, along with quality of life. Results identified subgroups of obese individuals who, in addition to BMI, shared common survey characteristics and were grouped as heavy-drinking males, younger healthy females, affluent healthy elderly, physically ill but happy elderly, unhappy anxious middle-aged, and a cluster with the poorest health.10

This study offers clinical relevance for targeting nutrition interventions to subgroups vs the general population of those with obesity. For example, discussing the role of alcohol in weight management with heavy-drinking males may be more appropriate than with young, healthy females. Similarly, affluent, healthy elderly wouldn’t necessarily need as extensive nutrition therapy as those in the poorest of health, where weight loss may not even be the primary focus.

Polygenic/Common Obesity
Genomewide association studies (GWAS) scan hundreds of thousands of genetic markers across thousands of complete sets of individuals’ DNA to find gene variations that may be related to a particular disease, such as those that play a role in obesity and other complex conditions. These tiny DNA differences, gene variants, or single-nucleotide polymorphisms often are related to disease risk. Some traits can be due to the simultaneous presence of DNA variation in multiple genes known as polygenic obesity, also referred to as common obesity.

The first obesity-related gene variant—fat mass and obesity associated (FTO) gene—was identified in 2007 on chromosome 16 and is fairly common.11 People who carry the FTO variant have a 20% to 30% higher risk of obesity than people who don’t have the variant.12 GWAS have identified more than 30 genes on 12 chromosomes that are associated with BMI.5

According to obesity expert Gabriel Smolarz, MD, MS, FACE, medical director at Novo Nordisk in Plainsboro, New Jersey, “The amount that genetics play a role in obesity is highly variable given the polygenic nature of common obesity.”

Monogenic Obesity
Genomewide linkage studies have identified genetic associations with rare, severe forms of obesity that are caused by mutations in a single gene, known as monogenic obesity. For example, Prader-Willi syndrome is caused by a mutation or chromosomal abnormality indicative of obesity and often accompanied by intellectual disability, reproductive anomalies, or other problems.5

Other monogenic mutations have been found in genes that play a significant role in appetite control, food intake, and energy homeostasis, mainly in genes that code for the hormone leptin.13 It’s the second obesity-associated gene variant to be identified on chromosome 18 close to the leptin receptor gene.14 Mediated by the central nervous system, leptin is secreted by white adipose tissue and inhibits food intake by signaling the hypothalamus to suppress appetite and stimulate energy expenditure.

While genes play a fundamental role in predisposing a person to obesity, the environment—particularly the readily available supply of calorie-dense foods and human lifestyle—can influence these genes both positively and negatively. It’s important to consider that even the most prominent FTO gene accounts for just a fraction of gene-related susceptibility to obesity,15 yet many people are convinced that nothing can be done about their genetic predisposition. Unfortunately, this is overly simplistic, as a healthful diet and physical activity can help to compensate for genetics.

A large meta-analysis explored data on individuals carrying the FTO gene and physical activity. Data from 218,000 adults showed that genetically susceptible adults who were physically active had almost a 30% lower risk of obesity compared with genetically susceptible adults who were physically inactive.16 This research demonstrates that those who carry the so-called obesity gene can benefit from physical activity.

Some obesity experts suggest that genetic screening for obesity is unhelpful, reasoning that some people believe what’s written into their genetic code is their destiny, leading to a fatalistic perspective and possible apathy about a healthful lifestyle.17 Genetic predisposition doesn’t necessarily change treatment options, such as physical activity and a healthful diet, for obesity and/or weight loss strategies. Furthermore, overemphasizing genes may distract from environmental and lifestyle factors that contribute to obesity.

According to J. Lennert Veerman, PhD, a professor of public health in the School of Medicine at the University of Sydney in Australia, genes may codetermine who develops obesity, but our environment determines how many develop it.17

It’s improbable that the rapid spread of obesity around the world is entirely due to genetics. Unlike the evolution of an obesogenic environment that’s occurred over the past several decades, the frequency of different genetic mutations across a population’s gene pool remains fairly stable for many generations. It takes time for new mutations or polymorphisms to spread.5

Supporting Patients
It’s now understood that body weight is more than a simple function of energy-in, energy-out, as both of these variables depend on many factors, such as metabolic, hormonal, and neural signals activated by food intake, as well as human behavior and the food environment.

Research on gene-environmental obesity is still in its infancy, but as early findings demonstrate, a person’s DNA isn’t necessarily their fate when it comes to healthy weight management. In fact, many people who carry genetic traits for obesity don’t have obesity or overweight due to environmental influences and healthful lifestyles.5 To be sure, genetics have a strong influence on every individual’s capacity for fat mass. Keeping this in mind, dietitians can best contribute to healthy weight management by putting into practice the following approaches:

Treat obesity as a disease. Since 2013, obesity has been classified as a disease by the American Medical Association. Despite decades of research documenting consistent stigma and discrimination against individuals with obesity, weight stigma is rarely considered in obesity prevention and treatment efforts.18 Although genes do play a fundamental role in predisposing a person to obesity, societal weight bias against individuals with obesity remains and even comes from patients’ own physicians. Unfortunately, obesity and nutrition aren’t widely covered in medical school curriculums.

As members of a health care team, RDs can help destigmatize obesity as a personality characteristic by participating in a new public narrative on obesity that’s consistent with evolving research. Obesity as a disease “also means challenging ourselves to speak differently,” Smolarz says.

For example, instead of saying someone “is obese,” it may be more appropriate to say they “have obesity,” Smolarz says. “We wouldn’t call a person who has cancer ‘cancerous.’”

Let patients know that we understand that adiposity is much more than a conscious choice and not a personal fault.

Counsel clients as individuals. Acknowledge heterogeneity for an individualized treatment approach. “We need to realize feelings of hunger or satiety are not voluntary sensations, no more than ignoring thirst after a trek through the desert,” Smolarz says.

The unique variation in genetics among populations with obesity has much clinical relevance. For example, consuming fried food has the potential to influence genes related to obesity.19 This emphasizes the need to educate those individuals who are genetically predisposed to obesity about their susceptibility and counsel them to minimize fried food intake.

In other research, physical activity and a healthful diet, including avoidance of sugar-sweetened beverages, can reduce expression of genetic variants for obesity.20

Encourage patients to develop a lifestyle plan to be practiced over the long term, and not a short-term diet approach with an impossible goal of perfection. Recruit patients to be partners in developing a plan that’s both effective and realistic. A goal to lose 10% of body weight for a person who has obesity can provide a plethora of health benefits.

“Sustained weight loss is so important in reducing complications across the board,” Smolarz says. “Losing 5% to 10% of weight, and keeping it off, can improve conditions like heart disease and diabetes, among others.”

Consider an initial restriction of 500 kcal per day from a patient’s estimated energy expenditure. Keep in mind that as patients get closer to meeting their weight loss goals, their basal metabolic rate also may decrease.

Prioritize minimally processed foods, as obesity may be caused by the changing nature of the food clients eat. More than 50% of the food supply in the United States is considered ultraprocessed. A diet of heavily processed foods triggers a significant intake in energy and subsequent weight gain, as much as a 2-lb increase in two weeks.21 The Mediterranean diet, without any fat or calorie restriction, has been shown to decrease body weight and lead to less gain in central adiposity compared with a control diet.22

Recommend regular physical activity. Exercise is paramount for any weight management plan, regardless of genetics. Data show that physical activity offsets the effects of the common variant of FTO.23 Subjects who carried the obesity-promoting gene and who were inactive had higher BMIs than people without the gene variant who were inactive. Having a genetic predisposition to obesity didn’t seem to matter for those who were active, as their BMIs didn’t differ from those who didn’t have the obesity gene.

The body has a homeostatic system that maintains body weight within a relatively narrow, individualized range. This regulatory system can counteract voluntary efforts to lose weight and maintain a healthy body weight by the activation of compensatory biological influences such as increased appetite or decreased metabolic rate.

For example, research shows that a 10% weight loss causes compensatory changes in energy expenditure.24 In severe obesity, voluntary efforts to eat less and move more have shown relatively modest effects on body weight.25 With significant fat loss, the body responds by lowering resting energy expenditure.26

“Your body defends your highest weight by making you feel hungrier and less full when you start losing weight,” Smolarz says.

Suggest patients improve sleep quality. Sleep deprivation increases the chances of developing
obesity, so it’s important to address the topic of sleep hygiene with individuals who may have a hard time losing excess weight. Insufficient sleep disrupts the balance of hormones, resulting in lower levels of the satiety-inducing hormone leptin and higher levels of the appetite-stimulating hormone ghrelin, triggering the desire for foods rich in fat and carbohydrate.2

In addition, people who get little sleep may have more opportunities to consume more calories simply by being awake longer. Finally, sleep-deprived people may complain of being too tired to engage in physical activity.

Final Thoughts
Research continues to consider the relationship between diet, genes, and obesity. Such information could reveal further strategies for obesity prevention and treatment. Most people likely have some genetic predisposition to obesity, but it becoming their destiny requires significant influences of environmental factors such as readily available calorie-dense, highly processed food 24/7, dramatic decreases in daily physical activity (especially in children), and an increase in sedentary activities (particularly screen time).5

As folk singer Mary Chapin Carpenter espouses with her lyrics, “We’ve got two lives: one we’re given and the other one we make.” To that end, RDs can support people with obesity with a lifelong practice of healthy weight management.

— KC Wright, MS, RDN, is a research-based nutritionist focusing on sustainable food systems and environmental influences for healthy people and the planet. Learn more about Wright at


1. Obesity and overweight. World Health Organization website. Updated April 1, 2020. Accessed May 10, 2020.

2. Healthy weight. Harvard T.H. Chan School of Public Health website. Accessed May 12, 2020.

3. Avila C, Holloway AC, Hahn MK, et al. An overview of links between obesity and mental health. Curr Obes Rep. 2015;4(3):303-310.

4. Rubino F, Puhl RM, Cummings DE, et al. Joint international consensus statement for ending stigma of obesity. Nat Med. 2020;26(4):485-497.

5. Genes are not destiny. Harvard T.H. Chan School of Public Health website. Accessed May 12, 2020.

6. Kelly T, Yang W, Chen CS, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond). 2008;32(9):1431-1437.

7. Heuer CA, McClure KJ, Puhl RM. Obesity stigma in online news: a visual content analysis. J Health Commun. 2011;16(9):976-987.

8. Farooqi S, O’Rahilly S. Genetics of obesity in humans. Endocr Rev. 2006;27(7):710-718.

9. Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997;27(4):325-351.

10. Green MA, Strong M, Razak F, Subramanian SV, Relton C, Bissell P. Who are the obese? A cluster analysis exploring subgroups of the obese. J Public Health (Oxf). 2016;38(2):258-264.

11. Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889-894.

12. Rajan KS, Permendra K, Kulandaivelu M. Molecular genetics of human obesity: a comprehensive review. C R Biol. 2017;340(2):87-108.

13. Hu F. Genetic predictors of obesity. In: Hu FB, ed. Obesity Epidemiology. New York: Oxford University Press; 2008:437-460.

14. Loos RJF, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40:768-775.

15. Walley AJ, Asher JE, Froguel P. The genetic contribution to non-syndromic human obesity. Nat Rev Genet. 2009;10(7):431-442.

16. Kilpeläinen TO, Lu Q, Brage S, et al. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLoS Med. 2011;8(11):e1001116.

17. Veerman JL. On the futility of screening for genes that make you fat. PLoS Med. 2011;8(11):e1001114.

18. Puhl R, Suh Y. Health consequences of weight stigma: implications for obesity prevention and treatment. Curr Obes Rep. 2015;4(2):182-190.

19. Qi Q, Chu AY, Kang JH, et al. Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies. BMJ. 2014;348:g1610.

20. Qi Q, Chu AY, Kang JH, et al. Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med. 2012;367(15):1387-1396.

21. Hall KD, Ayuketah A, Brychta R, et al. Ultra-processed diets cause excess calorie intake and weight gain: an inpatient randomized controlled trial of ad libitum food intake. Cell Metab. 2019;30(1):67-77.e3.

22. Estruch R, Martínez-González MA, Corella D, et al. Effect of a high-fat Mediterranean diet on bodyweight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial. Lancet Diabetes Endocrinol. 2019;7(5):e6-e17.

23. Andreasen CH, Stender-Petersen KL, Mogensen MS, et al. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes. 2008;57(1):95-101.

24. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332(10):621-628.

25. Wadden TA, Volger S, Sarwer DB, et al. A two-year randomized trial of obesity treatment in primary care practice. N Engl J Med. 2011;365(21):1969-1979.

26. Hall KD, Kerns JC, Brychta R, Knuth ND. Response to “Overstated metabolic adaptation after ‘The Biggest Loser’ intervention.” Obesity (Silver Spring). 2016;24(10):2026.